1. Field of the Invention
This invention relates to a method of heterocyclic synthesis, and in particular to a novel process for the preparation of substituted 2-aminopyrazine compounds, useful as intermediates in the preparation of insecticidal benzoylpyrazinylureas disclosed and claimed in Belgian Pat. No. 833288 (Mar. 11, 1976).
2. Description of the Prior Art
One of the main methods of synthesizing pyrazine compounds is by building up the pyrazine ring system from aliphatic components, and the essential step in most pyrazine syntheses from aliphatic components is formation of carbon-nitrogen bonds. Starting materials utilized can include .alpha.,.beta.-dicarbonyl compounds, .alpha.-aminocarbonyl compounds, .alpha.-aminonitriles, and .alpha.-halogenoketones.
In the prior art, Sharp et al., J. Chem. Soc. 932 (1951), describe the condensation of .alpha.-aminonitriles with oximinomethyl ketones to yield 3,5-disubstituted 2-aminopyrazine-1-oxides, which are then heated with sodium hydrosulphite to reduce the oxides to yield 3,5-disubstituted 2-aminopyrazines. This reference teaches that the efficiency of the general reaction is decreased by the replacement of alkyl with aryl groups.
In another reference, Taylor et al., J. Am. Chem. Soc. 95, 6407-6412 (1973), describe the preparation of 2-amino-3-carbamoyl-5-substituted-pyrazine-1-oxides, from the condensation of .alpha.-aminocyanoacetamide with an oximinoketone, for example, oximinoacetophenone or oximinoacetone, in glacial acetic acid solution. The products are used in pteridine syntheses.
Taylor et al., J. Am. Chem. Soc., 90, 2424 (1968), also describe the preparation of 2-amino-3-carbethoxy-5-methylpyrazine-1-oxide by the condensation of ethyl .alpha.-aminocyanoacetate with isonitrosoacetone (oximinoacetone) in glacial acetic acid. The product is also used in the synthesis of pteridines.
Yet another prior art reference is Lang et al., Tetrahedron Letters 3967-3970 (1974), which discloses a synthesis of aminopyrazines by condensation of the tosylate of the isonitroso derivative of malononitrile, or cyanoacetic ester, with a substituted enamine, followed by reaction of the condensation product with ammonia to yield the 2-amino-3,5,6-trisubstituted pyrazine. The products are alleged by Lang et al. to possess tuberculostatic and diuretic properties.
Also in the prior art is Masaki et al., Bull. Chem. Soc. Japan, 36, 922 (1963), which discloses the reaction of .alpha.-halo oximes with amines. The product thereby obtained is reductively cyclized using Raney nickel catalyst to yield a piperazinone.
Also included in the prior art are Masaki et al., J. Org. Chem. 29, 3165 (1964), and Masaki et al., J. Org. Chem. 31, 4143 (1966), both of which references disclose the reaction of protected .alpha.-aminohydroxamic acid with an .alpha.-chloro oxime, followed by removal of the oxime and O-benzyl groups, and treatment with ammonia to yield aspergillic acid-type compounds.
Another prior art reference is that of Masaki et al., Bull. Chem. Soc. Japan, 39, 2745 (1966), which teaches, inter alia, that the reaction of 1-chloro-2-oximino-3-butanone with aminoacetonitrile yields a mixture of N-(2-oximino-3-oxobutyl)aminoacetonitrile and N,N-bis(2-oximino-3-oxobutyl)aminoacetonitrile. These compounds were confirmed as the corresponding amidoxime and benzoyl or p-nitrobenzoyl derivatives, respectively. Ring closure of N-(2-oximino-3-oxobutyl)aminoacetonitrile by treatment with acids or by conversion of the nitrile into the iminoether was attempted, but the corresponding cyclic compound was not isolated.